Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients. Despite numerous advances in treatment, the prognosis for these patients is poor, with a median survival of 4-8 months. Whether a primary (intrinsic) malignancy, or a secondary (metastatic) malignancy, involvement of the brain in a cancer patient is devastating, because it threatens the very personality and identity of the individual, and is invariably the most likely of all complications to directly and severely affect the quality of life. Currently, the optimal treatment for most brain tumors involves primary surgical resection to facilitate adjuvant therapies such as radiation and chemotherapy. Despite the lack of class I evidence, it is widely agreed that surgery can improve the functional and vital prognosis when the resection is subtotal or better. The adage remains true that the smaller the "tumor burden", the more likely it is that adjuvant therapies will be beneficial. Unfortunately, many patients cannot undergo primary surgical resection of their brain tumor and therefore are destined to a poor outcome and premature demise. Reasons vary, but the two most important ones include an unfavorable location of the lesion, usual deep or otherwise inaccessible to conventional neurosurgical techniques, and poor general health of the patient, often seen with metastatic disease, that places the patient at an undue risk for complications from complex brain surgery and general endotrachial anesthesia. To address this problem, we propose to develop a MRI compatible "minimally invasive" neurosurgical intracranial robot (MINIR). As envisioned, MINIR will be under the direct control of a human operator, with targeting information obtained exclusively from frequently-updated MRI. Unlike currently available technology, MINIR will require only a very narrow "corridor" to approach and resect tumor, and will be capable of operating outside of the "line-of-site" of the entry trajectory. At its operating end, MINIR will be multi-digited, making it highly maneuverable, with all movements under dynamic control of a human operator. Like any human neurosurgeon currently, MINIR will resect tumor by positioning the end-probe comprised of, say, bi-polar electrocautery to liquify tissue. Dedicated irrigation and aspiration channels in the MINIR body will ensure washing out the debris and its removal. To realize MINIR, we will address the following specific aims: 1) Design a kinematically feasible MINIR with appropriate actuation and control strategy, 2) Develop and characterize a multi-piece mesoscale mold that is capable of: a) molding geometrically complex MINIR links with mesoscale features and b) performing in-mold assembly of bearings and actuators with the MINIR links, and 3) Validating the functionality, efficacy and safety of MINIR will require testing using both ex vivo and in vivo systems that model the expected human situation as closely as possible. [unreadable] PUBLIC HEALTH RELEVANCE: Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients with a median survival of 4-8 months. While surgical resection of the brain tumor is the preferred approach, most patients cannot undergo this procedure due to an unfavorable location of the lesion and poor general health. Hence, we propose to develop a magnetic resonance imaging (MRI) compatible "minimally invasive" neurosurgical intracranial robot (MINIR). [unreadable] [unreadable] [unreadable]